Joint Association of Sleep Onset Time and Sleep Duration With Cardiometabolic Health Outcome.

BACKGROUND: The association of sleep onset time and duration with cardiometabolic health is not well characterized. METHODS AND RESULTS: This study included 6696 adults aged 20 to 80 years from the NHANES (National Health and Nutrition Examination Study) 2015 to 2018. Participants were categorized into 9 groups according to the cross-tabulation of sleep onset time (<22:00 [early], 22:00-23:59 [optimal], and ≥24:00 [late]) and duration (<7 hours [insufficient], 7-8 hours [sufficient], and ≥9 hours [excessive]), with optimal sleep onset time and sufficient duration as the reference. The primary outcomes included hypertension, hypertriglyceridemia, low high-density lipoprotein cholesterol, hyperglycemia, central obesity, and metabolic syndrome. Inappropriate sleep onset time and sleep duration were associated with increased odds of hypertension, hypertriglyceridemia, and metabolic syndrome, especially among participants aged 40 to 59 years. Compared with men reporting optimal onset and sufficient duration, men reporting optimal onset with excessive duration (odds ratio [OR]: 2.01 [95% CI, 1.12-3.58]) and late onset with insufficient duration (OR, 1.74 [95% CI, 1.13-2.68]) had higher odds of metabolic syndrome. Compared with women reporting optimal onset and sufficient duration, women reporting optimal onset and insufficient duration (OR, 1.61 [95% CI, 1.11-2.32]) and early onset and excessive duration (OR, 2.16 [95% CI, 1.30-3.57]) had higher odds of hypertension, and women reporting late onset and excessive duration (OR, 5.64 [95% CI, 1.28-6.77]) were at the highest odds of hypertriglyceridemia. CONCLUSIONS: Late sleep onset as well as insufficient or excessive sleep duration are associated with adverse cardiometabolic outcomes, particularly in participants aged 40 to 59 years.

Schottky barrier reduction on optoelectronic responses in heavy ion irradiated WSe2 memtransistors.

Two-dimensional transition metal dichalcogenide-based memtransistors provide simulation, sensing, and storage capabilities for applications in a remotely operated aerospace environment. Swift heavy ion (SHI) irradiation technology is a common method to simulate the influences of radiation ions on electronic devices in space environments. Here, SHI irradiation technology under different conditions was utilized to produce complex defects in WSe2-based memtransistors. Low-resistance state to low-resistance state (LRS-LRS) switching behaviors under light illumination were achieved and photocurrent responses with different spike trains were observed in SHI-irradiated memtransistors, which facilitated the design of devices with enriched analog functions. Reduction of the Schottky barrier height due to the introduced defects at the metal/WSe2 interface was confirmed to be the major factor responsible for the observed behaviors. 1T phase and concentric circle-type vacancies were also created in the SHI-irradiated 2H-WSe2 channel besides the amorphous structure; these complex defects could seriously affect the transport properties of the devices. We believe that this work serves as a foundation for aerospace radiation applications of all-in-one devices. It also opens a new application field of heavy ion irradiation technology for the development of multiterminal memtransistor-based optoelectronic artificial synapses for neuromorphic computing.

Coaxial radiography guided puncture technique for percutaneous transforaminal endoscopic lumbar discectomy: A randomized control trial.

BACKGROUND: The coaxial radiography-guided puncture technique (CR-PT) is a novel technique for endoscopic lumbar discectomy. As the X-ray beam and the puncturing needle are maintained in a parallel and coaxial direction, the X-ray beam can be used to guide the trajectory angle, facilitating the choice of the puncture site and providing real-time guidance. This puncture technique offers numerous advantages over the conventional anterior-posterior and lateral radiography-guided puncture technique (AP-PT), especially in cases of herniated lumbar discs with a hypertrophied transverse process or articular process, high iliac crest, and narrowed intervertebral foramen. AIM: To confirm whether CR-PT is a superior approach to percutaneous transforaminal endoscopic lumbar discectomy compared to AP-PT. METHODS: In this parallel, controlled, randomized clinical trial, herniated lumbar disc patients appointed to receive percutaneous endoscopic lumbar discectomy treatment were recruited from the Pain Management Department of the Affiliated Hospital of Xuzhou Medical University and Nantong Hospital of Traditional Chinese Medicine. Sixty-five participants were enrolled and divided into either a CR-PT group or an AP-PT group. The CR-PT group underwent CR-PT, and the AP-PT group underwent AP-PT. The number of fluoroscopies during puncturing, puncture duration (min), surgery duration (min), VAS score during puncturing, and puncture success rate were recorded. RESULTS: Sixty-five participants were included, with 31 participants in the CR-PT group and 34 in the AP-PT group. One participant in the AP-PT group dropped out due to unsuccessful puncturing. The number of fluoroscopies [median (P25, P75)] was 12 (11, 14) in the CR-PT group vs 16 (12, 23) in the AP-PT group, while the puncture duration (mean ± SD) was 20.42 ± 5.78 vs 25.06 ± 5.46, respectively. The VAS score was 3 (2, 4) in the CR-PT group vs 3 (3, 4) in the AP-PT group. Further subgroup analysis was performed, considering only the participants with L5/S1 segment herniation: 9 patients underwent CR-PT, and 9 underwent AP-PT. The number of fluoroscopies was 11.56 ± 0.88 vs 25.22 ± 5.33; the puncture duration was 13.89 ± 1.45 vs 28.89 ± 3.76; the surgery duration was 105 (99.5, 120) vs 149 (125, 157.5); and the VAS score was 2.11 ± 0.93 vs 3.89 ± 0.6, respectively. All the above outcomes demonstrated statistical significance (P < 0.05), favoring the CR-PT treatment. CONCLUSION: CR-PT is a novel and effective technique. As opposed to conventional AP-PT, this technique significantly improves puncture accuracy, shortens puncture time and operation time, and reduces pain intensity during puncturing.

Organophosphate esters, airway inflammation, and lung function among U.S. participants: A nationally representative cross-sectional study from NHANES, 2011-2012.

BACKGROUND: Human beings are widespread exposed to organophosphate esters (OPEs), but little is known about their effects on respiratory health. OBJECTIVES: To investigate the associations of exposure to OPEs with lung function and airway inflammation among U.S. participants from NHANES, 2011-2012. METHODS: A total of 1636 participants aged 6-79 years were included. Concentrations of OPE metabolites were measured in urine and lung function was assessed with spirometry. Fractional exhaled nitric oxide (FeNO) and blood eosinophils (B-Eos), two important inflammatory biomarkers, were also measured. Linear regression was performed to examine the relationships of OPEs with FeNO, B-Eos and lung function. Bayesian kernel machine regression (BKMR) was used to evaluate the joint associations between OPEs mixtures and lung function. RESULTS: Three of seven OPE metabolites had detection frequencies > 80 %, including diphenyl phosphate (DPHP), bis (1,3-dichloro-2-propyl) phosphate (BDCPP), bis-2-chloroethyl phosphate (BCEP). A 10-fold increase in DPHP concentrations were associated with 1.02 mL decreases in FEV1 (ß = -0.01, 95 % CIs = -0.02, -0.003) and FVC (ß = -0.01, 95 % CIs = -0.02, -0.003), respectively, and the similar, modest decreases were seen for BDCPP. For each 10-fold increase in BCEP concentration, FVC was also reduced by 1.02 mL (ß = -0.01, 95 % CIs = -0.02, -0.002). Moreover, the negative associations were only found in non-smokers aged >35 years. The aforementioned associations were confirmed by BKMR, but we cannot definitively identify a constituent driving this association. B-Eos was negatively associated with FEV1 and FEV1/FVC, but not with OPEs. No associations were found of FeNO with OPEs and lung function. CONCLUSIONS: Exposure to OPEs was associated with modest decrements in lung function, although the observed decrease in FVC and FEV1 is unlikely to be of real clinical relevance for the majority of subjects in this series. Moreover, those associations presented age and smoking status-dependent pattern. Unexpectedly, the adverse effect was not mediated by FeNO/B-Eos.

Direct Fabrication of Sub-10 nm Nanopores in WO3 Nanosheets Using Single Swift Heavy Ions.

Extending the fabrication methodology of solid-state nanopores in a wide range of materials is significant in the fields of single molecule detection, nanofluidic devices, and nanofiltration membranes. Here, we demonstrate a new method to directly fabricate size- and density-controllable sub-10 nm nanopores in WO3 nanosheets using single swift heavy ions (SHIs) without any chemical etching process. By selecting ions of different electronic energy losses (Se), nanopores with sizes from 1.8 to 7.4 nm can be created in WO3 nanosheets. The creation efficiency of nanopores achieves ∼100% for Se > 20 keV/nm, and there exists a critical thickness below which nanopores can be created. Combined with molecular dynamics simulations, we propose that the viscosity and surface tension of the transient molten phase caused by SHIs are the key factors for the formation of nanopores. This method paves a way to fabricate solid-state nanopores in materials with a low viscosity and surface tension.

Assessment of right ventricular structure and systolic function in amateur marathon runners using three-dimensional speckle tracking echocardiography.

Prolonged high-intensity endurance exercise has been reported to have adverse effects on the heart, which are further correlated with exercise dose. However, its effect on the right ventricle (RV) of amateur runners is unknown. This study aimed was to evaluate the early right ventricular structure and systolic function of amateur marathon runners by three-dimensional speckle tracking echocardiography (3D-STE), and to further analyze the correlation between relevant parameters and the amount of training. A total of 30 amateur marathon runners (marathon group) and 27 healthy volunteers (control group) were enrolled. Conventional echocardiography combined with 3D-STE was performed in all subjects, and the marathon group was screened by echocardiography a week before a marathon (V1), within 1 h post-marathon (V2), and 4 days post-marathon (V3). RV global longitudinal strain (GLS) and RV end-diastolic volume (EDV) increased significantly in the marathon group compared to the control group (P < 0.05). RV GLS was significantly decreased in the marathon group within 1 h post-marathon (V1: - 26.2 ± 2.5% vs V2: - 23.0 ± 1.6% vs V3: - 25.6 ± 2.6%, P < 0.001). However, there was no significant difference in RV ejection fraction (RVEF) (P > 0.05). The results of the correlation analysis showed that RV EDV and RV end-systolic volume (ESV) were positively correlated with the average training volume (P < 0.001). Multivariate linear regression analysis showed that average training volume was an independent predictor of RV EDV in amateur marathoners (ß = 0.642, P < 0.001). The systolic function of the RV was enhanced in amateur marathon runners in the early stage, manifested by an increase in RV EDV. After a long period of high-intensity endurance exercise, RV systolic function will temporarily be reduced. 3D-STE can identify this subclinical change with high sensitivity and provide valuable information to assess the structure and function of RV in amateur marathon runners.

Association of perfluoroalkyl substances with pulmonary function in adolescents (NHANES 2007-2012).

Perfluoroalkyl substances (PFASs) constitute an environmentally persistent and widespread class of anthropogenic chemicals that have been used in industrial and commercial applications in the USA and around the world. Animal studies suggested its toxic impact on lung development, but the adverse effect of PFAS exposure on childhood pulmonary function has not been clearly determined. We investigated the potential cross-sectional association of environmental PFAS exposures with pulmonary function in 765 adolescents aged 12-19 years from the US National Health and Nutrition Examination Survey (NHANES) 2007-2012. Exposure to PFASs was estimated by measuring serum concentrations, and pulmonary function was assessed by spirometry. Linear regression and weighted quantile sum (WQS) regression were performed to estimate the associations of individual chemicals and chemical mixtures with pulmonary function. Median concentrations of PFOA, PFOS, PFNA, and PFHxS (detection frequencies > 90%) were 2.70, 6.40, 0.98, and 1.51 ng/mL, respectively. No associations were found between the four individual congeners and Σ4PFASs and the pulmonary function measures in total adolescents. Sensitive analyses were further conducted stratified by age (12-15 and 16-19 years) and sex (boys and girls). In adolescents aged 12-15 years, PFNA was negatively associated with FEV1:FVC (p-trend = 0.007) and FEF25-75% (p-trend = 0.03) among girls, while PFNA was positively associated with FEV1: FVC (p-trend = 0.018) among boys. No associations were found among adolescents aged 16-19 years, either boys or girls. The aforementioned associations were confirmed when further applying WQS models, and PFNA was identified to be the most heavily weighing chemical. Our results suggested that environmental exposure to PFNA may affect pulmonary function among adolescents aged 12-15 years. Given the cross-sectional analysis and less consistent results, further replications of the association in large prospective cohort studies are warranted.

A systematic and comprehensive analysis of T cell exhaustion related to therapy in lung adenocarcinoma tumor microenvironment.

Background: T cell exhaustion (TEX) is an important immune escape mechanism, and an in-depth understanding of it can help improve cancer immunotherapy. However, the prognostic role of TEX in malignant lung adenocarcinoma (LUAD) remains unclear. Methods: Through TCGA and GEO datasets, we enrolled a total of 498 LUAD patients. The patients in TCGA-LUAD were unsupervised clustered into four clusters according to TEX signaling pathway. WGCNA analysis, survival random forest analysis and lasso regression analysis were used to select five differentially expressed genes among different clusters to construct a TEX risk model. The risk model was subsequently validated with GEO31210. By analyzing signaling pathways, immune cells and immune checkpoints using GSEA, GSVA and Cibersortx, the relationship between TEX risk score and these variables was evaluated. In addition, we further analyzed the expression of CCL20 at the level of single-cell RNA-seq and verified it in cell experiments. Results: According to TEX signaling pathway, people with better prognosis can be distinguished. The risk model constructed by CD109, CCL20, DKK1, TNS4, and TRIM29 genes could further accurately identify the population with poor prognosis. Subsequently, it was found that dendritic cells, CD44 and risk score were closely related. The final single-cell sequencing suggested that CCL2O is a potential therapeutic target of TEX, and the interaction between TEX and CD8 + T is closely related. Conclusion: The classification of T cell depletion plays a crucial role in the clinical decision-making of lung adenocarcinoma and needs to be further deepened.

The Effect of Social Isolation on Sarcopenia: A Longitudinal Study among the Middle-Aged and Older Population in China.

INTRODUCTION: Although social isolation is associated with premature death and somatic and mental diseases, evidence of its long-term effect on sarcopenia is scarce. This study aimed to examine the longitudinal association between social isolation and possible sarcopenia. METHODS: We extracted baseline and 4-year follow-up data from the China Health and Retirement Longitudinal Study and included participants aged 45 years or above. Social isolation was measured by factors including living alone, marital status, frequency of contact with adult children and friends, and participation in social activity. The change in social isolation from baseline to follow-up was classified into stable, progressive, and regressive groups. Possible sarcopenia was detected using the handgrip strength and five-time chair-stand test. Using mixed-effects logistic regression, we studied the effect of baseline isolation and the change in isolation status on possible sarcopenia at a 4-year follow-up. RESULTS: A total of 5,289 participants aged 45-90 years and without possible sarcopenia at baseline were included. After 4 years, possible sarcopenia was detected in 21.7% (1,146/5,289) of the participants. Compared with the low social isolation group, the middle (OR = 1.53, 95% confidence interval [CI] = 1.16-2.04, p = 0.003) and high social isolation groups (OR = 1.65, 95% CI = 1.26-2.18, p < 0.001) were associated with a higher risk of possible sarcopenia. Being not married/cohabiting (OR = 1.58, 95% CI = 1.19-2.10, p = 0.002), lack of contact with children (OR = 1.86, 95% CI = 1.21-2.85, p = 0.004), and lack of social activities (OR = 1.26, 95% CI = 1.04-1.53, p = 0.019) were associated with an increased risk of possible sarcopenia. Compared with the stable social isolation group, the progressive group was associated with a greater risk of possible sarcopenia (OR = 1.51, 95% CI = 1.17-1.95, p = 0.001). CONCLUSIONS: Social isolation is associated with an increased risk of possible sarcopenia. Progressive social isolation further elevates the risk. The most vulnerable groups are middle-aged and older people who live alone, are not socially active, and lack contact with their children.

Prenatal pyrethroid exposure and lung function among school-aged children.

BACKGROUND: Previous epidemiological evidence mainly focused on the adverse effects of prenatal exposure to pyrethroid insecticides (PYRs) on respiratory health during childhood. It remains unclear whether the PYR exposures can also impact on children's lung function. OBJECTIVES: To explore the potential effects of prenatal PYR exposures on lung function in a population of Chinese children. METHODS: This study included 233 mother-child dyads from the Laizhou Wan Birth Cohort (LWBC), Shandong province, northern China, between September 2010 and December 2013. Three metabolites of PYRs [3-phenoxybenzoic acid (3-PBA), and cis- and trans-(2,2-dichlorovinyl)-2,2-dimethylcyclopropane-1-carboxylic acid (cis-DCCA and trans-DCCA)] were measured using gas chromatography-mass spectrometry (GC-MS) in maternal urine samples collected at recruitment. Lung function was assessed with spirometry in children aged 6-8 years. Multivariable linear regression and generalized linear models (GLMs) assessed the associations of prenatal PYR exposures with lung function in children. RESULTS: Among the PYR metabolites, 3-PBA (81.5%) were most frequently detected, followed by trans-DCCA (55.4%) and cis-DCCA (21.9%). The 3-PBA concentration was associated with a 1% decrease in FEV1/FVC in the highest quartiles of exposure compared to the lowest quartile, with a potential dose response association (p-trend = 0.085). Our findings provide a suggestive effect modification by sex, with girls being more susceptible than the boys (p-trend = 0.011). However, there were no associations between the trans-DCCA concentration and lung function parameters. CONCLUSION: Prenatal 3-PBA concentrations were associated with a modest decrease in FEV1/FVC among school-aged children, and the association was slightly more pronounced for the girls than for the boys.

Association between Mutations in Papain-like Protease (PLpro) of SARS-CoV-2 with COVID-19 Clinical Outcomes.

Papain-like protease (PLpro) is important for the replication and transcription of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This study aimed to reveal the PLpro mutations associated with the clinical outcomes of patients. Due to the importance of the S protein in the pathogenicity of SARS-CoV-2, the mutation of the S protein was also analyzed in this study. After downloading the data from the Global Initiative on Sharing Avian Influenza Data (GISAID) database, samples were divided into two groups on the basis of patient status, namely, recovered and dead groups. This study performed a univariate analysis and further explored the association of mutations with patient outcomes through multivariate logistic regression analysis. A total of 138,492 samples were used for analysis. The patients had a mean age of 43.66 ± 21.56 years, and 51.3% of them were female. Multivariate logistic regression results showed that, compared with men, women had a lower risk of dying from coronavirus disease 2019 (COVID-19) (OR = 0.687, 95%CI: 0.638-0.740). Compared with patients aged 17 years and younger, patients aged 18-64 years (OR = 2.864, 95%CI: 1.982-4.139) and patients over 65 years old (OR = 19.135, 95%CI: 13.280-27.572) had a higher risk of death after infection. Compared with the wild type, P78L (OR = 5.185, 95%CI: 2.763-9.730) and K233Q (OR = 5.154, 95%CI: 1.442-18.416) in PLpro were associated with an increased risk of death. A synergistic interaction existed between age and mutations A146D and P78L. The results of the multivariate logistic regression analysis of the data on vaccinated patients demonstrated that, compared with the wild type, the P78L (OR = 3.376, 95%CI: 2.040-5.585) mutation was associated with an increased risk of death. In conclusion, compared with the wild-type PLpro protein, the P78L and K233Q mutations may increase the risk of death in infected individuals. In addition, a synergistic effect existed between age and P78L and K233Q that increased the risk of death in older patients.

Performance of Imaging Techniques in Non-invasive Diagnosis of Non-alcoholic Fatty Liver Disease in Children: A Systematic Review and Meta-Analysis.

Background and Aim: Non-alcoholic fatty liver disease (NAFLD) has become the most common chronic liver disease in children. With the continuous emergence of various non-invasive diagnostic methods, imaging techniques have always been considered as potential alternative methods to liver biopsy. This study aimed to evaluate the diagnostic performance of imaging techniques so as to search for the most promising technology. Methods: We searched English and Chinese databases. English databases included Cochran library, Embase, PubMed, and Web of Science, while Chinese databases included the Wanfang database and China National Knowledge Internet. Results: Finally, 11 articles were included (12 studies, one of which included studies on both fibrosis and steatosis). Further, 26.2% of the participants had mild steatosis, 34.1% had moderate steatosis, and 34.9% had severe steatosis. Also, 64.0% had any fibrosis, 29.1% had significant fibrosis, 13.8% had advanced fibrosis, and 2.8% had cirrhosis. Irrespective of the grade of fibrosis, transient elastography (TE) had higher sensitivity (97-100%), whereas magnetic resonance elastography (MRE) had the lowest sensitivity (58-63%). The pooled sensitivity and specificity of imaging techniques in diagnosing steatosis were 89% (95% CI, 71-96) and 89% (95% CI, 72-96), and AUROC 0.95 (95% CI, 93-97), multifrequency magnetic resonance elastography-hepatic fat fraction (mMRE-HFF) had the highest sensitivity (87%, 95% CI 77-97), ultrasonography (US) had the lowest specificity (96%, 95% CI 92-98%). Conclusion: Imaging techniques have a good diagnostic performance for children with NAFLD, especially the diagnosis of liver fibrosis based on ultrasound or magnetic resonance elastography. Compared with different imaging techniques, TE has the best performance in diagnosing significant fibrosis. Liver stiffness measurement (LSM) is expected to become a biological indicator for routine screening, dynamic monitoring of disease changes, and prognostic evaluation.

Protective autophagy alleviates neurotoxin-gelsenicine induced apoptosis through PERK signaling pathway in Neuro-2a cells.

Gelsemium elegans Benth. (G. elegans) showed significant biological activities, but it has the side effects of neurotoxicity, predominantly in the form of respiratory depression. Gelsenicine is the main toxic constituent of G. elegans which is highly neurotoxic to humans and animals. Although the acute neurotoxicity of gelsenicine has been widely reported, but neurotoxicity mechanisms have not been elucidated and its direct effect on nerve cells remains poorly characterized. In this study, Neuro-2a cells were used to be our object of study for determining the mechanism by which gelsenicine induced neurotoxicity. We found that gelsenicine is neurotoxic to Neuro-2a cells; indeed cell proliferation was inhibited and apoptosis was induced in a dose-dependent manner. Meanwhile, gelsenicine markedly promoted autophagy and activated autophagic flux. Additionally, promoting autophagy with rapamycin decreased apoptosis, whereas blocking autophagy with 3-methyladenine (3-MA) increased apoptosis. Furthermore, the protein kinase ribose nucleic acid (RNA)-like endoplasmic reticulum kinase (PERK)/eukaryotic initiation factor 2 alpha (eIF2α)/activating transcription factor 4 (ATF4) signaling pathway was involved in the induction of protective autophagy in Neuro-2a cells. Inhibition of PERK using small interfering RNA (siRNA) inhibited gelsenicine-induced autophagy and aggravated apoptosis. These data indicate that gelsenicine not only exhibited cytotoxicity and induced apoptosis, but it also induced protective autophagy via PERK signaling pathway to alleviate gelsenicine-mediated apoptosis in Neuro-2a cells.

Urinary organophosphate metabolite concentrations and birth sizes among women conceiving through in vitro fertilization in Shanghai, China.

BACKGROUND: Few studies have examined the adverse birth sizes of preconception exposure to organophosphate pesticides (OPs) in women undergoing in vitro fertilization (IVF). OBJECTIVES: We investigated the relationship of preconception OP exposure with birth sizes among Chinese women undergoing IVF. METHODS: This study included 302 couples seeking infertility treatment in the China National Birth Cohort Study, from Shanghai, China, who gave birth to singleton infants between 2018 and 2021. Clinical data were collected from medical records. We measured the concentrations of six nonspecific dialkyl phosphates (DAP) metabolites of OPs [diethylthiophosphate (DETP), diethylphosphate (DEP), diethyldithiophosphate (DEDTP), dimethyldithiophosphate (DMTP), dimethylphosphate (DMP), and dimethyldithiophosphate (DMDTP)] in maternal urine. DMDTP and DEDTP were precluded from further analyses due to the low detection rates. Generalized linear models (GLMs) and weighted quantile sum (WQS) regression analyses were performed to examine the individual and joint effects of OP exposures on gestational age, birth weight, body length, and ponderal index. Odder ratio (OR) of preterm birth were estimated using logistic regression models. RESULTS: Women in the highest as compared with lowest quartile of DEP had shorter gestational age (ß = - 0.68; 95% CI = -1.24, -0.11). The association was modified by sex, with boys showing larger decreases in gestational age (ß = - 0.86; 95% CI = -1.60, -0.13). No associations were found between other DAP metabolites and birth sizes. Results from linear models with individual DAP metabolites were corroborated by the WQS regression where DEP had the largest contribution to the overall mixture effect on gestational age (weight = 0.70). Moreover, DEP concentration was associated with an elevated risk of preterm birth (OR = 1.35, 95% CI = 1.11, 2.25). CONCLUSION: Preconception DEP concentration was associated with shortened gestational age and increased risk of preterm birth, and the association was more pronounced among boys than girls.

Associations between exposure to a mixture of phenols, parabens, and phthalates and sex steroid hormones in children 6-19 years from NHANES, 2013-2016.

BACKGROUND: Humans are typically exposed to mixtures of environmental endocrine-disrupting chemicals simultaneously, but most studies have considered only a single chemical or a class of similar chemicals. OBJECTIVES: We examined the association of exposure to mixtures of 7 chemicals, including 2 phenols [bisphenol A (BPA) and bisphenol S (BPS)], 2 parabens [methylparaben (MeP) and propyl paraben (PrP)], and 3 phthalate metabolites [Mono-benzyl phthalate (MBzP), mono-isobutyl phthalate (MiBP), mono (carboxyoctyl) phthalate (MCOP)] with sex steroid hormones. METHODS: A total of 1179 children aged 6-19 years who had complete data on both 7 chemicals and sex steroid hormones of estradiol (E2), total testosterone (TT), and sex hormone-binding globulin (SHBG) were analyzed from the U.S. National Health and Nutrition Examination Survey 2013-2016. Free androgen index (FAI) calculated by TT/SHBG, and the ratio of TT to E2 (TT/E2) were also estimated. Puberty was defined if TT ≥ 50 ng/dL in boys, E2 ≥ 20 pg/mL in girls; otherwise prepuberty was defined. Linear regression, weighted quantile sum (WQS) regression, and Bayesian kernel machine regression (BKMR) were performed to estimate the associations of individual chemical or chemical mixtures with sex hormones. RESULTS: The linear regression showed that 2 phenols, 2 parabens, and 3 phthalate metabolites were generally negatively associated with E2, TT, FAI, and TT/E2, while positively with SHBG. Moreover, these associations were more pronounced among pubertal than prepubertal children. The aforementioned associations were confirmed when further applying WQS and BKMR, and the 3 phthalates metabolites were identified to be the most heavily weighing chemicals. CONCLUSIONS: Exposure to phenols, parabens, and phthalates, either individuals or as a mixture, was negatively associated with E2, TT, FAI and TT/E2, while positively with SHBG. Those associations were stronger among pubertal children.

De novo germline mutation in the dual specificity phosphatase 10 gene accelerates autoimmune diabetes.

Insulin-dependent or type 1 diabetes (T1D) is a polygenic autoimmune disease. In humans, more than 60 loci carrying common variants that confer disease susceptibility have been identified by genome-wide association studies, with a low individual risk contribution for most variants excepting those of the major histocompatibility complex (MHC) region (40 to 50% of risk); hence the importance of missing heritability due in part to rare variants. Nonobese diabetic (NOD) mice recapitulate major features of the human disease including genetic aspects with a key role for the MHC haplotype and a series of Idd loci. Here we mapped in NOD mice rare variants arising from genetic drift and significantly impacting disease risk. To that aim we established by selective breeding two sublines of NOD mice from our inbred NOD/Nck colony exhibiting a significant difference in T1D incidence. Whole-genome sequencing of high (H)- and low (L)-incidence sublines (NOD/NckH and NOD/NckL) revealed a limited number of subline-specific variants. Treating age of diabetes onset as a quantitative trait in automated meiotic mapping (AMM), enhanced susceptibility in NOD/NckH mice was unambiguously attributed to a recessive missense mutation of Dusp10, which encodes a dual specificity phosphatase. The causative effect of the mutation was verified by targeting Dusp10 with CRISPR-Cas9 in NOD/NckL mice, a manipulation that significantly increased disease incidence. The Dusp10 mutation resulted in islet cell down-regulation of type I interferon signature genes, which may exert protective effects against autoimmune aggression. De novo mutations akin to rare human susceptibility variants can alter the T1D phenotype.

Circular RNA 0014715 Facilitates Cell Proliferation and Inhibits Apoptosis in Esophageal Squamous Cell Carcinoma.

BACKGROUND: Circular RNAs (circRNAs) have recently been verified to have multiple biological functions and participate in diverse biological processes in different malignant tumors, including esophageal squamous cell carcinoma (ESCC). Nonetheless, the function of circular RNA 0014715 (hsa_circ_0014715, circ_0014715) in ESCC has not been described. MATERIALS AND METHODS: We investigated clinical data from sixty-seven patients undergoing surgery for esophageal cancer. The clinical data were collected. And we analyzed the correlation between the clinical characteristics of these patients and the expression of circ_0014715. Besides, we explored the expression of circ_0014715 in ESCC cell lines. We used cell counting kit-8, colony formation, transwell assay, and flow cytometry to detect changes in cell proliferation, migration, apoptosis, and cell cycle progression. RESULTS: We found that circ_0014715 was highly expressed in esophageal squamous cell carcinoma tissues and cell lines. The correlation analysis of clinicopathological features and gene expression revealed that high expression of circ_0014715 was related to nerve invasion, vascular invasion, more advanced tumor-node-metastasis (TNM) stage and poor differentiation grade. Receiver operating characteristic (ROC) curves revealed that circ_0014715 might have diagnostic value for ESCC. Experiments with cultured cells showed that knockdown of circ_0014715 significantly restrained cell proliferation, migration, invasion, wound healing and accelerated cell apoptosis. And cell cycle arrest at G2 phase was observed via flow cytometry. Overexpression of circ_0014715 caused the opposite effects. Collectively, these studies show that circ_0014715 is closely connected with the pathogenesis and development of ESCC. The excess expression of circ_0014715 may have promoting effects on the progression of esophageal cell carcinoma. CONCLUSION: Our finding revealed that circ_0014715 promoted tumor growth and cell proliferation. All of these suggest that targeting circ_0014715 has potential therapeutic value in the treatment of ESCC.

Genome-wide characterization of bZIP transcription factors and their expression patterns in response to drought and salinity stress in Jatropha curcas.

The basic leucine zipper (bZIP) family is one of the largest families of transcription factors (TFs) in plants and is responsible for various functions, including regulating development and responses to abiotic/biotic stresses. However, the roles of bZIPs in the regulation of responses to drought stress and salinity stress remain poorly understood in Jatropha curcas L., a biodiesel crop. In the present study, 50 JcbZIP genes were identified and classified into ten groups. Cis-element analysis indicated that JcbZIP genes are associated with abiotic stress. Gene expression patterns and quantitative real-time PCR (qRT-PCR) showed that four JcbZIP genes (JcbZIPs 34, 36, 49 and 50) are key resistance-related genes under both drought and salinity stress conditions. On the basis of the results of cis-element and phylogenetic analyses, JcbZIP49 and JcbZIP50 are likely involved in responses to drought and salinity stress; moreover, JcbZIP34 and JcbZIP36 might also play important roles in seed development and response to abiotic stress. These findings advance our understanding of the comprehensive characteristics of JcbZIP genes and provide new insights for functional validation in the further.

Caregivers: the potential infection resources for the sustaining epidemic of hand, foot, and mouth disease/herpangina in Guangdong, China?

BACKGROUND: Although several measures have been taken to control hand foot and mouth disease (HFMD) and herpangina (HA), these two diseases have been prevalent in China for 10 years with high incidence. We suspected that adults' inapparent infection might be the cause of the continued prevalence of HFMD/HA infection in mainland China. METHODS: To explore the role of adults (especially caregivers) in the transmission process of HFMD/HA among children, 330 HFMD/HA cases and 330 healthy children (controls) were selected for a case-control study. Then, data were analyzed by logistic regression. RESULTS: Single-variable analyses revealed that caregivers who tested positive for enterovirus was a significant risk factor of HFMD/HA transmission to children (adjusted odds ratio (OR) = 9.22; 95% CI, 1.16 to 73.23). In the final multivariable model, caregiver behavior, such as cooling children's food with mouth (OR = 1.85; 95% CI, 1.11 to 3.08) and feeding children with their own tableware (OR = 2.19; 95% CI, 1.07 to 4.45), significantly increased the risk of transmitting HFMD/HA to children. On the contrary, washing hands before feeding children reduced such risk. CONCLUSIONS: These results implied that the caregivers might be the infectious source or carriers of enterovirus. Therefore, preventing or treating the caregivers' enterovirus infection and improving their hygiene habits, especially when they are in contact with children, could provide a breakthrough for the effective control of HFMD/HA.

Willingness to Receive SARS-CoV-2 Vaccination and Associated Factors among Chinese Adults: A Cross Sectional Survey.

Vaccination is a key strategy to prevent the pandemic caused by the coronavirus disease 2019 (COVID-19). This study aims to investigate the willingness of Chinese adults to be vaccinated against COVID-19 and further explore the factors that may affect their willingness. We used a self-design anonymous questionnaire to conduct an online survey via the Sojump. A total of 1009 valid questionnaires were analyzed. The age of the participants ranged from 18 to 74. Among them, 609 (60.4%, 95%CI: 57.4-63.4%) were willing to receive the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine. Logistic regression analysis results showed that the age of 30-49 (OR = 2.042, 95%CI: 1.098-3.799), universities and colleges education (OR = 1.873, 95% CI = 1.016-3.451), master degree or above education (OR = 1.885, 95%CI = 1.367-2.599), previous influenza vaccination history (OR = 2.176, 95%CI: 1.474-3.211), trust in the effectiveness of the vaccine (OR = 6.419, 95%CI: 3.717-11.086), and close attention to the latest news of the vaccine (OR = 1.601, 95%CI: 1.046-2.449) were facilitative factors that affected their willingness to be vaccinated. More than half of the adults in China would be willing to receive a SARS-CoV-2 vaccine. Middle-aged people with higher education, those who had been vaccinated against influenza, and those who believed that COVID-19 vaccine was effective and paid close attention to it were more willing to be vaccinated. Our findings can provide reference for the implementation of vaccination and the prevention of COVID-19 in China. More studies are needed after the vaccine is launched.